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科学家研究艾滋病疫苗取得新进展

In 2009, a study in Thailand proved for the first time that an AIDS vaccine¹ was possible. But scientists were not sure why it offered some protection. Now they have some clues.

2009年，在泰国所做的一项研究首次证明，生产一种艾滋病疫苗是可能的。不过，当时科学家不大清楚的是，为什么这种疫苗对人体提供了一些保护。而现在，他们有了一些线索。

The Thailand study looked at a vaccine candidate called RV144. Since the results were announced, researchers have been combing through the data. What was it about this vaccine candidate that offered a protection rate of 31 percent? It was not high enough to go to market, but high enough to cause a lot of excitement for vaccine researchers.

泰国的这项研究考察了一种叫做RV144的候选疫苗。自从宣布研究结果以来，研究人员一直在仔细搜寻相关数据。为什么这种候选疫苗能提供31%的保护率呢？虽然这个比率还没有高到可以让这种候选疫苗进入市场的程度，但它却足以令那些疫苗研究人员兴奋不已。

“Once you have a vaccine that works, the next step in terms of the evolution of the vaccine is to try to first understand why it worked, with an idea that if we find out specifically what lab tests seem to correspond with protection we can design a new set of vaccines² that might provide better protection,” said Col. Jerome Kim, senior author of a new follow-up study on RV144.

关于RV144的一项新的后续研究报告的资深作者杰罗姆.金上校说：“一旦有了能起作用的疫苗，研发疫苗的下一步工作就是先搞清楚这种疫苗为什么奏效。因为如果我们通过实验室的测试查明这种疫苗的某个具体特性产生了保护作用，那么我们就能设计一批新的疫苗，它们可能会提供更好的保护。”

Antibodies

Kim, a medical doctor with the U.S. Military HIV Research Program, said when the RV144 results were announced scientists thought the success might be due to antibodies. These are proteins that bind³ to viruses and disable them.

杰罗姆.金上校是美军艾滋病毒研究计划的医生。他说，当RV144的结果被宣布时，科学家都认为这一成功可能是由于它产生的抗体。这些抗体由蛋白质构成，它们对病毒视而不见，而且使病毒失效。

“But we didn’t really know,” he said, “and so we looked very, very broadly at a number of different immune responses. And looking very broadly then allowed us to down-select – to pick out only those things which were the most important. Because that statistically⁴ gives us the greatest ability to say after all the testing’s done, this was important.”

杰罗姆.金上校说：“可是我们并不是真正了解这个问题。因此，我们从很多方面观察了一些不同的免疫反应。我们的观察面很宽，然后就缩小选择范围，从中挑出最重要的东西。因为在做完左右测试之后，统计数据使我们有能力做结论，这一点是重要的。”

The follow-up studies eventually led to two antibodies, one called IgG and the other IgA. Some in the Thai trial had more of one type of antibody than the other. Both, though, were drawn⁵ to a part of HIV called the envelope.

这些后续研究最终导致两种抗体的发现，一种叫做IgG，另一种叫做IgA。在泰国进行的试验中，有些试验里发现的一种抗体比另一种抗体多。不过，这两种抗体都被吸引到HIV包膜了。

Kim said, “HIV is a member of a group of viruses where the outer coat actually is composed of a little bit of what you call membrane⁶ and then what we call viral spikes⁷. And these viral spikes stick out of the membrane and envelope is contained in those spikes. And very often when vaccines work, the antibody is directed against these spikes because they’re prominent. They stick out and the immune system sees them and says, Ah ha! Let’s make an immune response against it.”

杰罗姆.金上校说：“艾滋病毒HIV是一组病毒中的一个成员，它的外层实际上是由薄膜构成的，然后就是薄膜上长的病毒刺突。这些病毒刺突从薄膜上突出来， HIV包膜就包含在这些刺突当中。当疫苗起作用时，抗体就被指示与那些突出的刺突作战。因为病毒刺突向外突出，所以免疫系统看到它们之后就说，哎，咱们要抵制刺突，产生免疫反应。”

But when it comes to HIV, Col. Kim said that’s easier said than done.

可是杰罗姆.金上校说，当对付艾滋病毒HIV时，那就是说到容易做到难了。

“The virus envelope is very variable. And it’s one of the reasons why we were so worried that no vaccine might ever be possible. Because like the flu virus, the HIV virus changes its envelope and does it very quickly, actually many times faster than the flu virus can,” he said.

杰罗姆.金上校说：“艾滋病毒包膜非常多变。这就是我们过去担心可能永远都找不到合适的疫苗的原因之一。因为就像流感病毒一样，艾滋病毒HIV改变它的包膜，并且变化的很快，比流感病毒变换包膜的速度快许多倍。”

A particular region of the envelope called V2 was the target of antibody response. This region may have something to do with how HIV mutates to avoid detection.

HIV包膜的一个被称为V2的特定区域是抗体反应的目标。这个区域或许与艾滋病毒为避免被发现而产生突变的方式有关。

“There is a part of the HIV envelope which exposed to the surface. So that’s very important because if it’s buried way, way down in the envelope the antibodies aren’t going to be able to reach it,” he said.

杰罗姆.金上校说：“HIV包膜的一部分暴露在表层。这一点十分重要。因为如果它埋在包膜的深层，各种抗体就无法接触它了。”

What’s going on?

The IgG and the IgA antibodies responded differently to the HIV envelope. But IgG was associated with a better vaccine protection rate by binding⁸ to the envelope V2 region. IgA, on the other hand, took a more broad approach to viral envelopes. Initially⁹, it was thought that this resulted in greater risk of infection. Kim says it was both unexpected and confusing, but it raised a number of hypotheses.

IgG和IgA抗体对HIV包膜做出不同的反应。可是，由于IgG抗体可以紧紧地依附在HIV包膜的V2区，它具有较好的疫苗保护率。另一方面，IgA抗体则与HIV包膜更多的地区接触。最初，人们认为这就导致更大的感染风险。杰罗姆.金上校说，这个问题既出人意料，又令人困惑，不过它使我们做出一些假设。

“They looked to see, is it actually making infection worse? And in fact it’s not. What it’s doing is it appears to potentially block the beneficial effects that were being seen with other immune responses. So it’s a blocking of the good response rather than something that increases the risk of infection,” he said.

杰罗姆.金上校说：“他们研究的是，这种情况是否造成更严重的感染呢？结论实际上并不是这样。IgA抗体所做的看起来可能是阻塞了我们在其他免疫反应中所看到的有益的效果。因此，它只是在阻塞良好的反应，而不是增加感染的风险。”

The antibodies were apparently¹⁰ competing with each other to bind to the envelope. Initial studies indicated IgA had a binding advantage over IgG. But Kim says that did not mean people were more likely to be infected with HIV.

这些抗体显然是为了依附在HIV包膜上而相互竞争。最初的研究显示，IgA抗体在依附HIV包膜方面比IgG抗体具有优势。可是杰罗姆.金上校说，这并不是说，据有这种抗体的人更可能感染艾滋病毒HIV。

“Really, the risk of HIV infection in people who had high levels of IgA was similar to the risk of infection to people who got placebos¹¹. They knocked down the beneficial response. They didn’t create a bad response,” he said.

杰罗姆.金上校说：“体内具有高含量IgA抗体的人感染艾滋病毒的风险与其他人感染艾滋病毒的风险差不多。IgA只是抑制了体内有益的反应，但它们并没有造成不良的反应。”

And that could be one reason why the efficacy rate of RV144 was not higher than 31 percent.

这也许是RV144疫苗的功效不高于31%的一个原因。

Kim said a lot more research is planned on the RV144 vaccine results, including follow-up studies. In fact, two trials are expected next year using similar vaccines. One would be tested in Thailand on the high risk group called men who have sex with men. The other would be tested against HIV Subtype C, which is a virus that’s predominantly found in southern Africa. Despite the vaccine breakthroughs, an effective AIDS vaccine is still considered years away.

杰罗姆.金上校说，他们计划对RV144疫苗的结果做更多的研究，包括后续研究。事实上，预料明年将使用类似的疫苗做两次试验。一次是在泰国进行，测试的对象是高风险群体男同性恋者。另一次试验要对艾滋病毒HIV的一种子类型C进行测试，这种艾滋病毒主要存在于非洲南部。尽管目前在艾滋病疫苗方面取得了突破，但是据认为研发出有效的艾滋病疫苗仍然需要若干年。